Membrane ultrafiltration: concentration of interleukin-3.

A pilot-plant-scale operation was used for studying membrane ultrafiltration and concentration of kiloliter quantities of the lymphokine interleukin-3 with a single set of membranes. Initial use of ammonium sulfate precipitation of interleukin-3 proved erratic in the recovery of biological activity and resulted in corrosion of the processing equipment. Membrane ultrafiltration proved to be effective in enabling control of the degree of concentration and predicting recovery of the biologically active protein.

Induction potential of Sendai virus and Newcastle disease virus for human lymphoblastoid interferon production.

Sendai and Newcastle disease viruses were tested for their induction potential in the production of human lymphoblastoid interferon [HuIFN-alpha(Ly)] from Namalva cell cultures. Tests were performed at multiple induction levels, for two induction periods, and on primed and nonprimed cell cultures. Sendai virus proved statistically more effective overall; priming and induction period had no significant effect.

The effect of calf serum on human lymphoblastoid cell-derived interferon production.

Substitution of low-cost calf serum for fetal bovine serum was evaluated in Namalva cell production of human alpha-lymphoblastoid interferon [HuIFN-alpha(Ly)] in 50-liter fermentors. Namalva cell growth and IFN yields were greatly reduced and protein precipitate weight increased from calf serum-supplemented cell cultures. The overall reduction in IFN production was greater than threefold, making the substitution impractical.

Large-scale production and concentration of human lymphoid interferon.

A stable and predictable production system is described for pilot plant quantities (milligram) of human lymphoid interferon, using suspension culture of an African Burkitt's lymphoma derived cell line Namalva with induction by Newcastle disease virus, B-1 strain. Cell cultures were grown in impeller-driven 50-liter fermentors with dilution of the postinduction culture using serum-free medium. High levels of dissolved oxygen were necessary for optimum cell growth. A total of 4,207 liters of interferon culture was produced in a series of 116 fermentor runs. An average yield of 3.5 log(10) international units of interferon per ml was realized before processing. Trichloroacetic acid was used to precipitate the interferon. An average of 3.35 log(10) international units of interferon per ml was recovered in the final nonpurified product.

Growth of pathogenic virus in a large-scale tissue culture system.

A model system is described for the mass propagation of Rift Valley fever (RVF) virus, utilizing large-volume fermentor units for suspension culture of tissue cells and the subsequent production of virus. Comparisons between laboratory- and fermentor-scale operations of tissue cell growth gave equivalent results. Cell viability dropped 24 to 30 hr postinfection with a subsequent virus yield between 10(8.0) and 10(9.0) mouse intracerebral median lethal doses per milliliter. Infecting volumes of tissue cell culture (20- or 40-liter working volumes) had no apparent effect on virus yields. Tissue cells grown under either oxidation-reduction potential- and pH-controlled or uncontrolled conditions showed little or no difference in their ability to produce RVF virus. We believe this tissue cell virus process to have potential application for large-scale production of vaccines for human or veterinary use or for the mass propagation of certain carcinogenic viruses for cancer research, once use of established lines for this purpose is accepted.

A neurological, ophthalmological and audiological survey of a suburban Jamaican community

A neurological, opthalmological and audiological survey was conducted in a suburban Jamaican community aged 35-74 years. One aim was to determine the prevalence of signs found in the Jamaican neuropathy syndrome and their association with sensorineural hearing loss and retrobulbar neuropathy. Mean hearing levels of Jamaicans were better than those reported from a comparable Scottish population. Conductive hearing losses, including otosclerosis, were uncommon. Sensorineural loss was found in 5.0 percent of men and 11.4 percent of women; presbyacusis was a possible cause in older subjects but in many the aetiology was unknown. Noise-induced hearing loss was not an important cause of impaired hearing. Refractive errors in vision were common and many needed proper correction. Pterygia were common (15.9 percent) but less prevalent among those of predominantly African origin, suggesting a racial difference in susceptibility. The prevalence of progressive cataract rose from 3.2 percent at 35-44 years to 71.7 percent at 65-74 years and was greater in diabetics than non-diabetics. Eight cases of chronic simple glaucoma were detected, a prevalence greater than that reported in a Welsh population. Tropical amblyopia (poor visual acuity, temporal pallor and field defects) was found in eight cases. Unexplained neurological signs, possibly representing manifestations of the Jamaican neuropathy syndrome, were found in 25 subjects (4.8 percent of females and 4.0 percent of males). Sensorineural hearing losses and retrobular neuropathy were common in these than in normal subjects but also occurred separately; it is unknown to what extent they are due to the same aetiology (AU)

In vivo growth and distribution of anthrax bacilli in resistant, susceptible, and immunized hosts.

Differences in in vivo growth rates of Bacillus anthracis in the bodies of infected rats and guinea pigs showed the effect of innate species resistance. The effect of two levels of immunity imposed on these hosts demonstrated that, as the degree of immunity increased, the growth rate of organisms decreased and was accompanied by a decrease in terminal population. It was shown that growth rates in the blood best reflected the population growth in the entire host. Data obtained from the naturally resistant rat that had been immunized with both the Belton-Strange protective antigen and live vaccine demonstrated the role of "toxins" in terminal anthrax. The in vivo morphological changes in anthrax bacilli pointed out errors regarding estimates of true terminal population of organisms when samples for counting were taken postmortem rather than at the time of death.

Antibiotic treatment of anthrax infection in mice.

Quantitative measurements of mean time to death, percentage of survivors, and viable cell populations in the whole body were employed to determine the effects of penicillin, dihydrostreptomycin, chlortetracycline, oxytetracycline, chloramphenicol, and antiserum on the course of anthrax infection in mice. By all parameters tested, penicillin and dihydrostreptomycin were most effective in the treatment of the disease. Therapy initiated in the later stages of the disease was more effective than that initiated in the earlier stages. Quantitative studies indicated that it was more difficult to eliminate organisms from the kidney than from any other organ or tissue. These measurements for the evaluation of antibiotic therapy are suggested for the study of other bacterial diseases.